In the debate on plastics and endocrine disruptor chemicals safety, policy lags behind science
… ” the regulatory and industry approach to determine chemical safety has been to determine whether chemicals act like poisons – and generally not whether they act like hormones. And some scientists are concerned that this could lead to false conclusions of safety.” …
… ” A trillionth of a gram of a hormone in a milliliter of blood …is enough to alter the course of development of tissue in the fetus and lead to disease later on in life, Until plastics are tested at such minute levels, he says, we are in the dark about what levels of exposure are safe — especially for babies developing in the womb. ” …
Sept 2014 Study Abstract
Here we demonstrate that Bisphenol A (BPA) exposure during a time point analogous to the second trimester in humans has real and measurable effects on brain development and behavior. Furthermore, our study is the first, to our knowledge, to show that bisphenol S, a replacement used in BPA-free products, equally affects neurodevelopment. These findings suggest that BPA-free products are not necessarily safe and support a societal push to remove all structurally similar bisphenol analogues and other compounds with endocrine-disruptive activity from consumer goods. Our data here, combined with over a dozen physiological and behavioral human studies that begin to point to the prenatal period as a BPA window of vulnerability, suggest that pregnant mothers limit exposure to plastics and receipts.
Jan 2014 Study Abstract
We measured serum dBPA in non-pregnant and pregnant female rhesus monkeys, fetuses and amniotic fluid. dBPA was administered by a daily oral bolus or sc implantation of Silastic capsules; both resulted in daily average serum unconjugated dBPA concentrations of <1ng/ml. We observed lower serum concentrations of unconjugated dBPA in pregnant females relative to pre-pregnancy values, and generally lower concentrations in fetal serum than in maternal serum. Differences in pharmacokinetics of dBPA were evident between pre-pregnancy, early and late pregnancy, likely reflecting changes in maternal, fetal and placental physiology. The serum ratio of conjugated to unconjugated dBPA after continuous sc release of dBPA was similar to values reported in human biomonitoring studies and markedly lower than with oral administration, suggesting oral bolus exposure is not an appropriate human exposure model. We report elsewhere that there were numerous adverse effects on fetuses exposed to very low serum dBPA in these studies.
Sources and more information
Very easy to read and very well documented, full of link studies links, read In The Debate On Plastics Safety, Policy Lags Behind Science, SoundMedicine, APR 13, 2015.
Bisphenol A (BPA) pharmacokinetics with daily oral bolus or continuous exposure via silastic capsules in pregnant rhesus monkeys: Relevance for human exposures, NCBI PMID:24582107, 2014 Jun;45:105-16 , sciencedirect, doi:10.1016/j.reprotox.2014.01.007, Reproductive Toxicology, Volume 45, June 2014.
Low-dose exposure to bisphenol A and replacement bisphenol S induces precocious hypothalamic neurogenesis in embryonic zebrafish, pnas, doi: 10.1073/pnas.1417731112, September 16, 2014.
New ingredient in plastic bottles, receipts has same effect on lab animals as the old chemical does
Exposure to bisphenol-S (BPS), an ingredient that has replaced BPA in many items, caused irregular heartbeats in female lab rats, according to the study by Hong-Sheng Wang and colleagues published this 26 February 2015. The findings were “remarkably similar—if not identical to—what we find in BPA” Wang said.
Bisphenol S (BPS) is increasingly been used as a substitute for BPA in some “bisphenol A (BPA)-free” consumer goods and in thermal papers. Wide human exposure to BPS has been reported; however, the biological and potential toxic effects of BPS are poorly understood.
Objective: To elucidate the sex-specific rapid impact of BPS in rat hearts and its underlying mechanism.
Rapid effects of BPS in rat hearts were examined using electrophysiology, confocal and conventional fluorescence imaging, and immunoblot.
In female rat hearts, acute exposure to 10-9 M BPS increased heart rate and in the presence of catecholamine-induced stress condition, markedly increased the frequency of ventricular arrhythmia events. BPS increased the incidence of arrhythmogenic triggered activities in female ventricular myocytes, and altered myocyte Ca2+ handling, particularly spontaneous Ca2+ release from the sarcoplasmic reticulum. The dose responses of BPS’ actions were inverted-U shaped. The impact of BPS on myocyte Ca2+ handling was mediated by estrogen receptor β signaling and rapid increases in the phosphorylation of key Ca2+ handling proteins including ryanodine receptor and phospholamban. The pro-arrhythmic effects of BPS were female-specific; male rat hearts were not affected by BPS at the organ, myocyte and protein levels.
Rapid exposure to low-dose BPS has pro-arrhythmic impact on female rat hearts; these effects at the organ, cellular and molecular levels are remarkably similar to those reported for BPA. Evaluation of the bioactivity and safety of BPS and other BPA analogs is necessary before they are used as BPA alternatives in consumer products.
Sources and more information
Chemical in BPA-Free Products Linked to Irregular Heartbeats, nationalgeographic news, FEBRUARY 25, 2015.
Rapid Responses and Mechanism of Action for Low-Dose Bisphenol S on ex Vivo Rat Hearts and Isolated Myocytes: Evidence of Female-Specific Proarrhythmic Effects, Environ Health Perspect; DOI:10.1289/ehp.1408679, 26 February 2015, full study PDF.
It is very clear we have to set up a different system to better protect the brains of the future
“ The numbers are startling. According to the U.S. Centers for Disease Control and Prevention, about 1.8 million more children in the U.S. were diagnosed with developmental disabilities between 2006 and 2008 than a decade earlier. During this time, the prevalence of autism climbed nearly 300 percent, while that of attention deficit hyperactivity disorder increased 33 percent. CDC figures also show that 10 to 15 percent of all babies born in the U.S. have some type of neurobehavorial development disorder. Still more are affected by neurological disorders that don’t rise to the level of clinical diagnosis. “
Chemicals and the Brain
Something in the Air
The Stress Factor
What to Do?
Read: What are we doing to our childrens brains,
by Elizabeth Grossman, on ensia, February 16, 2015.
and from the same author: Banned in Europe, safe in the U.S., ensia., June 9, 2014.
Summary Health Statistics for U.S. Children: National Health Interview Survey, 2009, cdc.
Children’s Exposure to Mercury Compounds, who, 2010.
National Report on Human Exposure to Environmental Chemicals, cdc, 2009 and 2015.
Low-dose exposure to bisphenol A and replacement bisphenol S induces precocious hypothalamic neurogenesis in embryonic zebrafish
Bisphenol A, known as BPA, is a chemical produced in massive quantities around the world for use in consumer products, including household plastics. In response to public concerns, many manufacturers have replaced bisphenol A with a chemical called bisphenol S (BPS), which is often labelled as “BPA-free” and presumed to be safer.
In a new study, researchers in Deborah Kurrasch’s lab at the University of Calgary have provided evidence that BPA and BPS cause alterations in brain development leading to hyperactivity in zebrafish.
“I was actually very surprised at our results. This was a very, very, very low dose, so I didn’t think using a dose this low could have any effect,” says Kurrasch, PhD, a researcher in the University of Calgary’s Cumming School of Medicine and corresponding author on the paper.
For the study, Kurrasch worked with University of Calgary researcher Hamid Habibi, PhD, and Cassandra Kinch, a PhD student, to expose zebrafish embryos to concentrations of the chemicals at levels found in the Bow and Oldman rivers of southern Alberta. By doing this, exposure to BPA and BPS changed the timing when neurons were formed in the brains of the zebrafish.
Prenatal period a particularly sensitive stage
“These findings are important because they support that the prenatal period is a particularly sensitive stage, and reveals previously unexplored avenues of research into how early exposure to chemicals may alter brain development,” says Kinch.
“In the second trimester, brain cells become the specialized neurons that make up our brain. What we show is that the zebrafish exposed to BPA or BPS were getting twice as many neurons born too soon and about half as many neurons born later, so that will lead to problems in how the neurons connect and form circuits,” says Kurrasch, a member of the Alberta Children’s Hospital Research Institute and the Department of Medical Genetics.
Change in behaviour detected
Researchers discovered the number of neurons generated in the developing zebrafish brains increased by 180 per cent compared with unexposed fish. They also learned that BPS increased the number of neurons by 240 per cent in similar experiments. The result was a change in behaviour, with the fish demonstrating greater hyperactivity later in life.
Another surprise finding was that zebrafish receptors targeted by BPA and BPS to mediate this early neuronal birth in zebrafish brains were androgen receptors. Assumptions based on numerous reports postulated that BPA and BPS modulate normal physiology by mimicking the endogenous sex steroid estrogen, and not testosterone.
“Finding the mechanism linking low doses of BPA to adverse brain development and hyperactivity is almost like finding a smoking gun,” says Habibi, a professor of environmental toxicology and comparative endocrinology in the Faculty of Science.
A caution for pregnant women
Although further research is needed to explore that link and the potential effect on human brains developing in the womb, Kurrasch says the findings add weight to other studies suggesting pregnant women should try to limit their exposure to items containing bisphenols. The evidence also supports removing all bisphenols and structurally similar chemicals from consumer products, she says.
Zebrafish are a widely accepted biomedical model for understanding embryonic brain development. About 80 per cent of the genes found in people have a counterpart in zebrafish — and possess very similar developmental processes as humans.
Sources and more information
Zebrafish study shows bisphenols affect embryonic brain development, University of Calgary, January 13, 2015.
Researchers find BPA and BPS affect embryonic brain development in zebrafish, eurekalert, 12-JAN-2015.
Low-dose exposure to bisphenol A and replacement bisphenol S induces precocious hypothalamic neurogenesis in embryonic zebrafish, pnas, January 12, 2015.
BPA alternative disrupts normal brain-cell growth, is tied to hyperactivity, study says, washingtonpost, January 12, 2015.
BPS is just as potent as BPA in altering brain development and causing hyperactive behavior. It also disrupts heart rhythms, alters cell proliferation leading to cell death…
Currently, no federal agency tests the toxicity of new materials before they are allowed on the market… ! ? ! ?
Common BPA substitute, BPS, disrupts heart rhythms in females
” … In the current study, the investigators perfused, or flowed, BPS through the arteries of each animal’s pumping heart, after stimulating the heart with the hormone catecholamine to mimic stress. For a control group, 30 rat hearts received only catecholamine and no BPS.
Exposure to BPS rapidly increased the heart rate of female rats and under the stress condition led to arrhythmias—heart rhythm abnormalities—far greater than in the control rats that did not receive BPS, Wang reported. Electocardiograms demonstrated that BPS caused extra heartbeats and a racing heartbeat, also known as ventricular tachycardia. In male rats, BPS reportedly did not have this rapid impact on the heart… ”
Exposure to BPA Substitute Causes Hyperactivity and Brain Changes in Fish
” …At the peak time of neuronal birth, the number of neurons in BPA-exposed fish rose 170 percent compared with unexposed fish, Kurrasch stated. In similar experiments using BPS, the number of neurons in exposed fish increased 240 percent. These results, she explained, suggest that BPA and BPS could lead to altered brain connections and might explain the hyperactivity they observed in another experiment. Specifically, the research team used movement tracking software to evaluate behavioral changes in young fish and found that fish exposed during brain development to either BPA or BPS were hyperactive, but unexposed fish were not… ”
Bisphenol S Disrupts Estradiol-Induced Nongenomic Signaling in a Rat Pituitary Cell Line: Effects on Cell Functions
Background: Bisphenol-A (BPA) is a well-known endocrine disruptor that imperfectly mimics the effects of physiologic estrogens via membrane-bound estrogen receptors (mERα, mERβ, and GPER/GPR30), thereby initiating nongenomic signaling. Bisphenol S (BPS) is an alternative to BPA in plastic consumer products and thermal paper.
To characterize the nongenomic activities of BPS, we examined signaling pathways it evoked in GH3/B6/F10 rat pituitary cells alone and together with the physiologic estrogen estradiol (E2). Extracellular signal-regulated kinase (ERK)– and c-Jun-N-terminal kinase (JNK)–specific phosphorylations were examined for their correlation to three functional responses: proliferation, caspase activation, and prolactin (PRL) release.
We detected ERK and JNK phosphorylations by fixed-cell immunoassays, identified the predominant mER initiating the signaling with selective inhibitors, estimated cell numbers by crystal violet assays, measured caspase activity by cleavage of fluorescent caspase substrates, and measured PRL release by radioimmunoassay.
BPS phosphoactivated ERK within 2.5 min in a nonmonotonic dose-dependent manner (10–15 to 10–7 M). When combined with 10–9 M E2, the physiologic estrogen’s ERK response was attenuated. BPS could not activate JNK, but it greatly enhanced E2-induced JNK activity. BPS induced cell proliferation at low concentrations (femtomolar to nanomolar), similar to E2. Combinations of both estrogens reduced cell numbers below those of the vehicle control and also activated caspases. Earlier activation of caspase 8 versus caspase 9 demonstrated that BPS initiates apoptosis via the extrinsic pathway, consistent with activation via a membrane receptor. BPS also inhibited rapid (≤ 1 min) E2-induced PRL release.
BPS, once considered a safe substitute for BPA, disrupts membrane-initiated E2-induced cell signaling, leading to altered cell proliferation, cell death, and PRL release.
Most Plastic Products Release Estrogenic Chemicals: A Potential Health Problem That Can Be Solved
Chemicals having estrogenic activity (EA) reportedly cause many adverse health effects, especially at low (picomolar to nanomolar) doses in fetal and juvenile mammals.
We sought to determine whether commercially available plastic resins and products, including baby bottles and other products advertised as bisphenol A (BPA) free, release chemicals having EA.
We used a roboticized MCF-7 cell proliferation assay, which is very sensitive, accurate, and repeatable, to quantify the EA of chemicals leached into saline or ethanol extracts of many types of commercially available plastic materials, some exposed to common-use stresses (microwaving, ultraviolet radiation, and/or autoclaving).
Almost all commercially available plastic products we sampled—independent of the type of resin, product, or retail source—leached chemicals having reliably detectable EA, including those advertised as BPA free. In some cases, BPA-free products released chemicals having more EA than did BPA-containing products.
Many plastic products are mischaracterized as being EA free if extracted with only one solvent and not exposed to common-use stresses. However, we can identify existing compounds, or have developed, monomers, additives, or processing agents that have no detectable EA and have similar costs. Hence, our data suggest that EA-free plastic products exposed to common-use stresses and extracted by saline and ethanol solvents could be cost-effectively made on a commercial scale and thereby eliminate a potential health risk posed by most currently available plastic products that leach chemicals having EA into food products.
Sources and More Information:
Common BPA substitute, BPS, disrupts heart rhythms in females, Endocrine Society, Newsroom, 23-Jun-2014.
Exposure to BPA Substitute Causes Hyperactivity and Brain Changes in Fish, Endocrine Society, Newsroom, 23-Jun-2014.
Bisphenol S Disrupts Estradiol-Induced Nongenomic Signaling in a Rat Pituitary Cell Line: Effects on Cell Functions, Environ Health Perspect., DOI:10.1289/ehp.1205826, March 2013.
Most Plastic Products Release Estrogenic Chemicals: A Potential Health Problem That Can Be Solved, Environ Health Perspect., PMC3222987, Jul 1, 2011.
In this recent Korean study, adult zebrafish pairs were exposed to Bisphenol-S (BPS) for 3 weeks. A significant decrease of egg production in female fish and a significant decrease of testosterone concentration in male fish were observed.
While bisphenol S (BPS) has been frequently detected both in environment and biota, limited information is available on its effects on endocrine system. In the present study, adult zebrafish pairs were exposed to 0.5, 5, and 50 μg/L of BPS for 21 d, and the effects on reproduction, sex hormones, and transcription of the genes belonging to hypothalamic-pituitary-gonad (HPG) axis were investigated. Adverse effects on performances of F1 generation were further examined with or without subsequent exposure to BPS. Egg production and the gonadosomatic index in female fish were significantly decreased at ≥0.5 μg/L BPS. Plasma concentrations of 17β-estradiol were significantly increased in both male and female fish. In male fish, however, significant decreases of testosterone concentration were observed along with up-regulation of cyp19a, and down-regulation of cyp17 and 17βhsd transcripts. Parental exposure to BPS resulted in delayed and lesser rates of hatching even when they were hatched in control water. Continuous BPS exposure in F1 embryos resulted in worse hatchability and increased malformation rates compared to those without BPS exposure. Our observations showed that exposure to low level BPS could affect the feedback regulation of HPG axis of zebrafish and impair the hatching and development of its offspring.
Bisphenol S Disrupts Estradiol-Induced Nongenomic Signaling in a Rat Pituitary Cell Line: Effects on Cell Functions
Just like the controversial Bisphenol A that it designed to replace, Bisphenol S chemical used in cash register receipts and other consumer products messes with hormones, according to research by University of Texas scientists. The study is the first to link low concentrations of BPS – a BPA alternative – to disruption of estrogen, spurring concern that it might harm human health. Researchers exposed rat cells to levels of BPS that are within the range people are exposed to…. and, just like BPA, the compound interfered with how cells respond to natural estrogen, which is vital for reproduction and other functions.